The alpha 1-->3 fucosylation at the penultimate GlcNAc catalyzed by fucosyltransferase VII is blocked by internally fucosylated residue in sialosyl long-chain poly-LacNAc: enzymatic basis for expression of physiological E-selectin epitope.
Sialosyl-fucosyl poly-LacNAc without sialosyl-Lex epitope in myeloid cell line HL60 was shown to be the ligand for E-selectin-dependent adhesion, particularly under dynamic flow conditions, in our previous study (Handa K, Stroud MR, Hakomori S, Biochemistry 36, 12412-12420, 1997). HL60 cells express only fucosyl-transferase (FT) IV and VII. X3NeuAcVII3FucnLc10, a representative component showing E-selectin-dependent binding under dynamic flow conditions, is not alpha 1-->3 fucosylated at the penultimate GlcNAc catalyzed by FT-VII, but is alpha 1-->3 fucosylated at the internal GlcNAc catalyzed by FT-IV. VI3NeuAcnLc6 is converted to VI3NeuAcIII3FucnLc6 by FT-IV, but is also converted to VI3NeuAcV3FucnLc6 by FT-VII. Thus, penultimate fucosylation catalyzed by FT-VII is not restricted for nLc6 backbone, but is highly restricted for nLc10 backbone. The cooperative effect of FT-IV and FT-VII for synthesis of poly-LacNAc having sialosyl-Lex with internal fucosylation may be blocked or highly restricted in poly-LacNAc having more than two LacNAc units, because preferential alpha 1-->3 fucosylation by FT-IV takes place at internal GlcNAc, inhibiting penultimate fucosylation by FT-VII.
Handa
K
K
Division of Biomembrane Research, Pacific Northwest Research Foundation, Seattle, Washington, USA.
Withers
D A
DA
Hakomori
S
S
D000117:Acetylglucosamine / Q000378:metabolism*; D001483:Base Sequence; D002240:Carbohydrate Sequence; D017931:DNA Primers / Q000235:genetics; D019040:E-Selectin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000939:Epitopes / Q000737:chemistry; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000187:drug effects / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009504:Neutrophils / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
D017931:DNA Primers; D019040:E-Selectin; D000939:Epitopes; D008024:Ligands; D009844:Oligosaccharides; D011134:Polysaccharides; D000080506:Sialyl Lewis X Antigen; D005643:Fucose; C037199:poly-N-acetyllactosamine; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase; D019158:N-Acetylneuraminic Acid; D000117:Acetylglucosamine